Improving Insulin Sensitivity in Patients With Type 2 Diabetes Via Repeated Cold-induced Shivering Thermogenesis

NCT07573917 | Recruiting

• 1 other identifier: 2025-5718
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Type 2 Diabetes Mellitus (T2DM) is a widespread health condition characterized by impaired ability of the body to maintain glucose homeostasis. This impairment often leads to secondary complications, including heart disease, high blood pressure, and poor quality of life. While exercise and healthy eating are effective strategies in managing and preventing T2DM, data shows that long-term adherence to these methods are poor - especially among elderly, individuals with obesity and/or with physical limitations. This clinical study explores cold exposure with shivering as a novel strategy to improve blood sugar control and heart health. In earlier research, spending time in mildly cold environments (around 15-17°C) for a few hours a day improved insulin sensitivity of T2DM patients. Interestingly, these benefits only occurred when the cold caused mild shivering. In a recent 10-day cold acclimation study with overt shivering for minimally 1 hour/day, we observed improved glucose tolerance in participants with overweight/obesity, as well as improved fasting lipid profiles. These results indicate that when accompanied with sufficient level of muscle activation, repeated exposure to cold can beneficially affect both glucose and lipid levels - both of which are impaired in people with T2DM. In this study, we hypothesise that a 10-day cold acclimation with shivering will improve the (peripheral) insulin sensitivity of patients with T2DM, accompanied by enhanced skeletal muscle FA uptake and oxidation as assessed via the 11C palmitate uptake.

Conditions

Type 2 Diabetes

Keywords

Insulin sensitivity; Substrate metabolism; shivering thermogensis; cardiometabolic health

Outcome Measures

Primary Outcomes (1)

• Whole-body insulin sensitivity measured as glucose infusion rate (GIR) in µmol/kg/min during the stable period of the low- and high-insulin phase of the clamp.

  1\) Hepatic insulin sensitivity measured as percent EGP suppression in µmol/kg/min; 2) Peripheral insulin sensitivity measured as Rd in µmol/kg/min. Determined by means of a hyperinsulinaemic-euglycaemic clamp.

  At baseline and Day 13.

Secondary Outcomes (1)

• 11-C palmitate uptake and oxidation in liver and skeletal muscle, expressed in µmol/g/min

  At Day 3 and Day 12.

Other Outcomes (9)

• 24-hour systolic and diastolic blood pressure and heart rate

  24-hour period before the baseline clamp (i.e. visit 2) and 24-hour period after the post-acclimation clamp (i.e. visit 13).

• Plasma metabolites

  Day 2 and Day 13 for insulin stimulated conditions, and Day 3 and Day 12 for cold-stimulated conditions.

• Average 24-hour interstitial glucose concentrations

  24-hour period before Day 2 and after Day 13.

Study Arms (1)

Cold acclimation with shivering

EXPERIMENTAL

This is a single-arm longitudinal study with a 10-day cold acclimation intervention period. Pre- and post-intervention measurements will be obtained before and after the 10-day period.

Behavioral: Cold exposure with shivering

Interventions

Cold exposure with shivering BEHAVIORAL

Cold exposure which elicits a minimally 80% increase in the baseline metabolic rate of participants.

Cold acclimation with shivering

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients are able to provide signed and dated written informed consent prior to any study specific procedures
• Women are post-menopausal (defined as at least 1 year post cessation of menses)
• Aged ≥ 40 years and ≤ 75 years
• Patients should have suitable veins for cannulation or repeated venipuncture
• Body mass index (BMI) 25-38 kg/m2
• Stable dietary habits (no weight loss or gain \>5kg in the past 3 months)
• Diagnosed with T2D at least 1.5 years before the start of the study
• Relatively well-controlled T2D: HbA1c \< 8.5%
• No signs of active diabetes-related co-morbidities like active cardiovascular diseases, active diabetic foot, polyneuropathy or retinopathy
• No signs of active liver or kidney malfunction

You may not qualify if:

• Previous enrolment in a clinical study with an investigational product during the last 3 months or as judged by the Investigator
• Participate in sports of physical activity at a moderate- to high-intensity more than 3 times a week, or as judged by the investigator
• Being cold-acclimated, e.g. having taken daily extended cold baths, working in a refrigerated environment, or practicing regular cold-water swimming/ showering within 1 month of starting the study
• Unstable body weight (weight gain or loss \> 5 kg in the last three months)
• Alcohol consumption of \>2 servings per day for man and \>1 servings per day for women
• Smoking
• Being insulin-dependent and/or using SGLT2 inhibitor medications
• Patients with congestive heart failure and and/or severe renal and or liver insufficiency
• Men: Hb \<8.4 mmol/L, Women: Hb \<7.8 mmol/l
• A medical doctor will judge participation eligibility based on the medical history questionnaire, medication use and fasting blood parameters. If the medical doctor advises that a patient cannot participate, the patient will be excluded from enrolment.
• Being pregnant
• Having participated in another study involving PET/CT scanning in the past 1 year

Sponsors & Collaborators

• Université de Sherbrooke: lead
• Maastricht University Medical Center: collaborator

Study Sites (1)

Centre de recherche du CHUS

Sherbrooke, Quebec, J1H 5N4, Canada

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Insulin Resistance

Interventions

Shivering

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism

Intervention Hierarchy (Ancestors)

Thermogenesis; Body Temperature Regulation; Body Temperature; Physiological Phenomena; Homeostasis; Adaptation, Physiological; Adaptation, Biological; Biological Phenomena

Study Officials

• Denis P. Blondin, PhD

  Université de Sherbrooke

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Frédérique Frisch

CONTACT

819-346-1110; frederique.frisch@usherbrooke.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate professor

Study Record Dates

• First Submitted: September 9, 2025
• First Posted: May 7, 2026
• Study Start: September 24, 2025
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): May 31, 2027
• Last Updated: May 7, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share

Locations

CA (1)